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[Effects of timolol and carteolol on ocular pulsatile blood flow].

Effects of timolol (0.5%) and carteolol (2%) on ocular pulsatile blood flow (PBF) were studied in healthy adult volunteers. PBF was measured with the BFA system, analyzing the ocular pressure waves. Each drug was instilled in one eye and PBF was measured in both eyes before and fifteen minutes after the instillation. In each drug, the PBF change between the two measurements was evaluated with a control study, which was performed in the same manner with physiological saline solution. In the non-instilled eyes, both timolol (n = 6) and carteolol (n = 9) had no significant change on PBF. In the instilled eyes, timolol (n = 6) caused no significant change, whereas carteolol (n = 9) increased PBF significantly. The range of the BFA system measurement error was within 4.7 +/- 2.4 microliters/min (P = 95%). Taking the error into account in each instilled eye, timolol (n = 6) increased PBF in 3 eyes and decreased it in 3 eyes, while carteolol (n = 9) increased PBF in 7 eyes, did not change it in one eye and decreased it in one eye. It is thought the effect of carteolol to increase PBF may be explained by endothelium-dependent relaxing factor (EDRF).

Adult↗

Pulsatile coronary flow determination by digital angiography.

A new angiographic method to calculate absolute coronary arterial blood flow and its cyclic variations as a function of time, has been designed and evaluated. The method combines densitometric analysis of spatial and temporal aspects concerning the contrast propagation through the arterial system from digital images, and is based on applying the concept of conservation of contrast material in successive images. It requires a standard arteriographic procedure. In simulations with both constant as well as pulsatile flow through a coronary arterial phantom, an excellent agreement with electromagnetic flow measurements was demonstrated (r = 0.993 and r = 0.982, respectively). Preliminary clinical results show, that the method yields reproducible assessment of coronary flow patterns after repeated injections in a patient. In a coronary artery bypass graft, coronary flow patterns in a baseline and a drug-induced hyperemic state were obtained. A consistent coronary flow reserve value was determined after repeated examinations. The method has been shown to be feasible in clinical applications, uncomplicated and fast, but requires further animal and clinical validation in order to determine the possible applications, limitations and accuracy.

Coronary Angiography↗

Large curvature effect on pulsatile entrance flow in a curved tube: model experiment simulating blood flow in an aortic arch.

We measured the velocity profiles of pulsatile entrance flow in a strongly curved tube using a laser-Doppler anemometer in order to simulate blood flow in the aortic arch under various conditions, i.e., a ratio of tube to curvature radius of 1/3, Womersley parameters of 12 and 18, and peak Dean number up to 1200. Axial isovelocity contours of the cross-section showed the potential vortex to be near the entrance, and with the maximum velocity there being skewed towards the inner wall; thereafter shifting towards the outer wall. During the deceleration phase, reverse axial flow occurred near the inner wall, and a region of this flow extended downstream. The large curvature contributes to the enhancement of the secondary flow and flow reversal, which elevates the wall-shear stress oscillations. The location of elevated wall-shear oscillations corresponds to the vessel wall region where atherosclerotic formation frequently occurs; thereby indicating that both the large curvature and pulsatility play key roles in formation of localized atherosclerotic lesions.

Aorta, Thoracic↗

Noninvasive analysis of renal artery blood flow dynamics with MR cine phase-contrast flow measurements.

It was the aim of this study to quantify the measurement of pulsatile flow in the renal artery with the noninvasive magnetic resonance cine phase-contrast (MRCPC) method and combine it with the simultaneous assessment of pulsatile flow with a transit-time ultrasound (TTUS) flowmeter. In seven foxhounds with a chronically implanted precalibrated TTUS flow probe, MRCPC flow measurements were made in the renal artery with a temporal resolution of 32 ms. Mean and pulsatile flow signal were compared by the simultaneous ipsi- or contralateral measurement of the renal blood flow signal by both methods (TTUS and MRCPC). In addition, comparative MRCPC and TTUS flow measurements were made with artificial renal artery stenosis and after the administration of angiotensin II. The mean flow data assessed by the noninvasive MRCPC flow measurements showed an excellent correlation with corresponding TTUS recording (r = 0.99). The MRCPC flow signal displayed a waveform of the renal artery flow profile that was very similar to the TTUS flow pulse. The hemodynamic changes induced by angiotensin II or due to renal artery stenosis were also reliably detected by MRCPC. MRCPC provides a reliable noninvasive method for the quantification of mean blood flow and the assessment of the pulsatile flow signal in the renal artery and proves to be sensitive to hemodynamic changes of pathophysiological importance. Alternatively, the method may be used for studies in physiology that demand a noninvasive approach.

Angiotensin II↗

Microcontinuum model for pulsatile blood flow through a stenosed tube.

The effects of polar nature of blood and pulsatility on flow through a stenosed tube have been analysed by assuming blood as a micropolar fluid. Linearized solutions of basic equations are obtained through consecutive applications of finite Hankel and Laplace transforms. The analytical expressions for axial and particle angular velocities, wall shear stress, resistance to flow and apparent viscosity have been obtained. The axial velocity profiles for Newtonian and micropolar fluids have been compared. The interesting observation of this analysis is velocity, in certain parts of cycle, for micropolar fluid is higher than Newtonain fluid. Variation of apparent viscosity eta a with tube radius shows both inverse Fahraeus-Lindqvist and Fahraeus-Lindqvist effects. Finally, the resistance to flow and wall shear stress for normal and diseased blood have been computed and compared.

Arterial Occlusive Diseases↗

Effects of compression bandaging on leg pulsatile blood flow.

Leg external compression bandaging is the mainstay of venous ulcer treatment, yet little is known about the impact of therapeutic compression levels on arterial haemodynamics. In this study, the effect of foot-to-knee, four-layer compression bandaging on below-knee arterial pulsatile blood flow was assessed by nuclear magnetic resonance flowmetry. In 14 healthy supine subjects bilateral flow measurements at five below-knee sites without compression, and after compressing one leg to an average malleolar sub-bandage pressure of 40.7 +/- 4.0 mmHg, revealed a potentially important new phenomenon. The forefoot-to-knee compression bandaging caused a highly significant (P < 0.001) increase in the bandaged leg pulsatile blood flow owing to increases in both peak flow and pulse width. It is hypothesized that arteriolar vasodilatation, induced either myogenically by reduced transmural pressure or by vasodilatory substance release triggered by increased venous shear stress, produce the observed compression-related phenomenon. Whatever the mechanism(s), the finding of a compression-associated pulsatile flow increase suggests a previously undiscovered arterial linkage, which may play a role in the well-documented beneficial effects of compression bandaging in venous ulcer treatment. A possible impact of the arterial flow-pulse increase is speculated to effect venous ulcer outcome via a decrease in leucocyte effects in the distal microvasculature, as a consequence of the more vigorous haemodynamic state.

Adult↗

Assessment of tumor hemodynamics in small hepatocellular carcinoma: comparison of Doppler ultrasonography, angiography-assisted computed tomography, and pathological findings.

AIM: We evaluated the usefulness of Doppler ultrasonography (DUS) for the analysis of tumor hemodynamics in small hepatocellular carcinoma (HCC). METHODS: We compared Doppler ultrasound (DUS) findings with angiography-assisted computed tomography (Angio-CT) such as CT during arterial portography and during hepatic arteriography in the evaluation of the intratumoral hemodynamics, and with pathologic findings in 45 small HCC nodules (< or =3.0 cm in diameter) of 43 patients. DUS flow pattern of each nodule was categorized into three types: afferent continuous flow (Type 1), afferent pulsatile flow with afferent continuous flow (Type 2), and afferent pulsatile flow without afferent continuous flow (Type 3). Intratumoral blood supply was determined by Angio-CT, and pathologic findings were evaluated on resected or biopsied specimen. RESULTS: Based on Angio-CT findings, Type 1 nodules showed decreased arterial blood supply (ABS) without decreased portal blood supply (PBS). Type 2 nodules showed unchanged ABS but decreased PBS. Type 3 nodules showed both increased ABS and decreased PBS. DUS findings well represented blood supply of HCC evaluated by Angio-CT. In addition, all Type 1 and 2 nodules were well-differentiated HCC, and all Type 3 nodules were moderately or poorly differentiated HCC; DUS findings well reflected differentiation of HCC. CONCLUSIONS: DUS is a non-invasive imaging method and can be used for the evaluation of the stage of malignancy of small HCC.

Aged↗

Pulsatile blood flow from impeller pump: a dream has come true.

For decades many investigations have been made on producing a pulsatile blood flow with an impeller pump. It has been foiled because of excessive hemolysis. Other investigators foretold that a pulsatile centrifugal pump is impossible in the near future, without increasing the complexity of the system remarkably. The author has presevered in this study and made progress steadily. An axial pulsatile impeller pump with constant-rotating speed was developed, in which the impeller reciprocates along its axis while rotates. Meanwhile, a pulsatile implantable impeller centrifugal pump is now in animal surviving experimental stage. The pulsatility of the blood flow is achieved by changing the rotating speed of the impeller periodically, via introducing a square wave form voltage into the motor coil. The hemodynamic and physiological superiorities to both nonpulsatile impeller pump and diaphragm pump were demonstrated. The hematological and biochemical data indicated low hemolysis and thrombogenesis, low renal and heptic dysfunction. Furthermore, a pulsatile implantable impeller total heart has completed its acute biventricular assist animal experiments. This is an almost unique total heart at the present, it is driven by a single motor, the left and right pumps eject the blood simultaneously, and the volume equilibrium of both pumps is achieved naturally. The dream of producing a pulsatile blood flow with an impeller pump has come true. Doubtlessly, an impeller heart with simplicity, pulsatility, implantability, compatibility and reliability, will be a viable alternative to diaphragm heart, really.

Animals↗

LDA measurements and numerical prediction of pulsatile laminar flow in a plane 90-degree bifurcation.

An experimental and numerical study of pulsatile laminar flow in a plane 90-degree bifurcation is presented. Detailed LDA velocity measurements of the oscillatory flow field have been carried out. The numerical predictions, which are based on an iterative, finite-difference numerical procedure using primitive dependent variables, are in good agreement with the measurements. The results show that one separation zone is established near the bottom wall of the main duct and another near the upstream wall of the branch. The location and size of the separation zones vary within the cycle and are influenced by the Reynolds number, the flow rate ratio, and the Stokes number.

Arteries↗

Measurement of coronary flow using high-frequency intravascular ultrasound imaging and pulsed Doppler velocimetry: in vitro feasibility studies.

The recent development of intravascular ultrasound imaging offers the potential to measure blood flow as the product of vessel cross-sectional area and mean velocity derived from pulsed Doppler velocimetry. To determine the feasibility of this approach for measuring coronary artery flow, we constructed a flow model of the coronary circulation that allowed flow to be varied by adjusting downstream resistance and aortic driving pressure. Assessment of intracoronary flow velocity was accomplished using a commercially available end-mounted pulsed Doppler catheter. Cross-sectional area of the coronary artery was measured using a 20 MHz mechanical imaging transducer mounted on a 4.8 F catheter. The product of mean velocity and cross-sectional area was compared with coronary flow measured by timed collection in a graduated cylinder by linear regression analysis. Excellent correlations were obtained between coronary flow calculated by the ultrasound method and measured coronary flow at both ostial (r = 0.99, standard error of the estimate [SEE] = 13.9 ml/min) and distal (r = 0.98, SEE = 23.0 ml/min) vessel locations under steady flow conditions. During pulsatile flow, calculated and measured coronary flow also correlated well for ostial (r = 0.98, SEE = 12.7 ml/min) and downstream (r = 0.99, SEE = 9.3 ml/min) locations. That the SEE was lower for pulsatile as compared with steady flow may be explained by the blunting of the flow profile across the vessel lumen by the acceleration phase of pulsatile flow. These data establish the feasibility of measuring coronary artery blood flow using intravascular ultrasound imaging and pulsed Doppler techniques.

Coronary Circulation↗

Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging.

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm2, respectively.

Adult↗

Endotoxemia and cytokine generation in cardiac surgery in relation to flow mode and duration of cardiopulmonary bypass.

We investigated whether pulsatile flow in cardiopulmonary bypass (CPB), which has been shown to improve intestinal perfusion, reduces endotoxin translocation from the gut and, in consequence, decreases cytokine generation. The study population consisted of 48 adult patients who underwent elective CPB surgery. Pulsatile flow was used during aortic cross-clamping in 24 patients and nonpulsatile flow in 24 patients. Plasma endotoxin concentration increased in all patients during CPB. Significantly (P < 0.05) lower peak levels of 8.25 +/- 1.17 (SEM) pg/mL were reached 30 min after CPB in patients with pulsatile flow in contrast to 11.26 +/- 1.42 pg/mL in patients with nonpulsatile flow. The extent of endotoxemia was not related to the duration of CPB. Following the increase of plasma endotoxin, the concentrations of IL-6 and IL-8 increased with delay of approximately 1 h. The peak levels of these cytokines corresponded significantly (P < 0.005 and P < 0.01, respectively) with duration of CPB, but not with flow mode. Thus, in patients with CPB of more than 97 min (median), IL-6 reached a peak of 335.5 +/- 48.87 pg/mL and IL-8 of 64.86 +/- 24.79 pg/mL in contrast to 210.9 +/- 18.45 pg/mL and 21.2 +/- 10.19 pg/mL, respectively, with bypass times of less than 97 min. The degree of endotoxemia in CPB mainly depends on the quality of tissue perfusion. Cytokine generation, however, is not triggered exclusively by endotoxin, but rather by the trauma of CPB and surgery.

Aged↗

Endothelial cell dynamics under pulsating flows: significance of high versus low shear stress slew rates (d(tau)/dt).

Shear stress modulates endothelial cell (EC) remodeling via realignment and elongation. We provide the first evidence that the upstroke slopes of pulsatile flow, defined as shear stress slew rates (positive d(tau)/dt), affect significantly the rates at which ECs remodel. We designed a novel flow system to isolate various shear stress slew rates by precisely controlling the frequency, amplitude, and time-averaged shear stress (tau(ave)) of pulsatile flow. Bovine aortic endothelial cell (BAEC) monolayers were exposed to three conditions: (1) pulsatile flow (1 Hz) at high slew rate (293 dyn/cm2 s), (2) pulsatile flow (1 Hz) at low slew rate (71 dyn/cm2s), and (3) steady laminar flow at d(tau)/dt = 0. All of the three conditions were operated at tau(ave) = 50 dyn/cm2. BAEC elongation and alignment were measured over 17 h. We were able to demonstrate the effects of shear stress slew rates ((tau)/dt) on EC remodeling at a fixed spatial shear stress gradient (d(tau)/dx). We found that pulsatile flow significantly increased the rates at which EC elongated and realigned, compared to steady flow at d(tau)/dt = 0. Furthermore, EC remodeling was faster in response to high than to low slew rates at a given tau(ave).

Animals↗

Compression-induced pulsatile blood flow changes in human legs.

Initial and sustained (7-h) impacts of foot-to-knee compression bandaging on leg arterial pulsatile blood flow were assessed by nuclear magnetic resonance flowmetry in eight healthy supine subjects. A widely used bandaging method (zinc impregnated gauze + Coban) and a slight variant (Coban only) were applied one week apart to one leg. Blood flow was measured on each day of bandage application before and after bandaging and after 7 h of normal activity. Initial mean sub-bandage pressures (lateral gaiter) were between 28.4 and 28.9 mmHg but were significantly reduced after 7 h to 16.3-19.4 mmHg. Overall below-knee pulsatile blood perfusion was initially significantly increased by both methods mainly due to increased proximal blood flow. Bandaging was also associated with a decrease in blood perfusion of the nonbandaged control leg mainly due to a decrease in distal blood flow. Neither of these effects were sustained after 7 h. The fact that neither sub-bandage pressure nor blood flow was sustained may indicate a causal linkage, a concept consistent with the finding of a linear relationship between afternoon blood flow and sub-bandage pressure reductions. The implications of the present findings for venous ulcer therapy are speculative and based on the concept that arterial pulsatile flow augmentation is a positive feature. If so, more frequent bandage changes to provide transient flow stimulation or use of bandages to better maintain sub-bandage pressure to sustain flow increases may be useful.

Adult↗

Does the technique of cardiopulmonary bypass affect lung water content?

Several efforts have been made to improve the technique of cardiopulmonary bypass (CPB), including the use of pulsatile flow and the modification of cannulation technique. The present study focused upon extravascular lung water (EVLW) in 60 aortocoronary bypass patients subjected to four different perfusion techniques during CPB: group 1 (n = 15): non-pulsatile flow and standard cannulation; group 2 (n = 15); pulsatile flow and standard cannulation; group 3 (n = 15): nonpulsatile flow and monoatrial cannulation (i.e., always "partial" bypass during CPB); group 4 (n = 15): pulsatile flow and monoatrial cannulation. EVLW content was measured using the double-indicator dilution technique with indocyanine green; in addition, various hemodynamic and laboratory variables were measured. Lung water content rose above normal values (mean: 5.79 +/- 0.33 ml/kg) only in the groups submitted to the standard cannulation technique, irrespective of whether the perfusion flow was pulsatile or not (group 1: + 27.4%; group 2: + 25.5%). Pulmonary gas exchange, too, was compromised only in these patients (PaO2 in group 1 -19% and in group 2 -17%; Qs/Qt in group 1 + 36 rel. % and in group 2 + 29 rel. %), whereas all patients with monoatrial cannulation and partial bypass throughout the CPB period showed no rise in EVLW content or Qs/Qt and no drop in PaO2. From the results of this study we conclude that pulsatile perfusion during open heart surgical procedure has no advantages in regard to lung water content. Monoatrial cannulation with partial bypass at all times during CPB, however, seems to be beneficial, probably owing to the maintenance of pulmonary circulation during the bypass period.

Aged↗

Comparative clinical study of pulsatile and non-pulsatile perfusion in 350 consecutive patients.

Pulsatile perfusion has been shown to offer significant haemodynamic advantages over non-pulsatile perfusion in many experimental studies. Clinical acceptance of pulsatile perfusion during cardiac surgical procedures has, however, been hampered by the lack of technologically satisfactory pulsatile pump systems, and by inadequate clinical experience of routine use of pulsatile perfusion. The recent introduction of reliable pulsatile pump systems with low haemolysis characteristics has made possible the clinical validation of the previous experimental studies. We describe the results of a prospective study of mortality, haemodynamic morbidity, and haematological status, in 350 consecutive adult patients submitted to cardiopulmonary bypass procedures in a surgical unit over a 12-month period. One hundred and seventy five patients were perfused with conventional non-pulsatile flow and 175 with pulsatile flow, using a modified roller-pump pulsatile system (Cobe-Stockert). The groups were closely similar in terms of preoperative characteristics, referral category, and pathology requiring surgery. Operative techniques, bypass parameters, and anaesthetic regime were standardised in both groups. The results were as follows. (1) Total mortality was significantly lower in the pulsatile group (4.6%) compared with the non-pulsatile group (10.3%), p = 0.06. (2) The incidence of deaths attributable to post-perfusion low cardiac output was significantly lower in the pulsatile group (1.1% compared with 6.3%, p = 0.02). (3) Requirement for mechanical (intra-aortic balloon) or drug circulatory support was significantly lower in the pulsatile group. (4) The use of pulsatile perfusion was not associated with any increase in haemolysis, blood cell depletion, or postoperative bleeding problems.

Adult↗

[Counterpulsation by means of a new device with a pulsatile blood flow in open heart operations (author's transl)].

A new counterpulsation method in operations on an open heart is described. Clinical experience in the use of the new device in 124 patients, which also makes it possible to produce a pulsatile flow of blood in the system of extracorporeal circulation, testifies to its effectiveness. The authors claim that the positive changes in cardiac output, diastolic and systolic pressure, and coronary circulation are among the factors which cause an improvement in the final result of the operation in patients with severe valvular diseases and ischemic heart disease.

Adult↗

Patterns of flow in the left coronary artery.

The purpose of this investigation is to describe our preliminary observations of the overall pattern of flow in a mold of the left coronary artery of a pig. Flow in the coronary mold was visualized by the injection of dye into the sinus of Valsalva. Studies were performed during steady flow at rates of 100, 200, 300, 400, and 500 mL/min. Studies were also performed during pulsatile flow, using a pulse duplicator that simulated the magnitude and phasic pattern of coronary flow at rest and during reactive hyperemia. At conditions that simulated rest, mean coronary flow was adjusted to 121 mL/min of which 24 mL/min (20 percent) was systolic. During simulated reactive hyperemia, mean flow was 440 mL/min. Visualization of flow revealed the absence of disturbances of turbulence during both steady and pulsatile flow in the left anterior descending (LAD) and left circumflex (CIRC) coronary arteries throughout the entire range of flow studied. Prominent spiraling of flow occurred during steady and pulsatile flow. Spiraling of flow was not observed in the LAD at rest during pulsatile flow, but developed during simulated reactive hyperemia. Helical flows were observed in the CIRC both during simulated rest and reactive hyperemia. These observations suggest that helical flows may be characteristic features of flow in the left coronary artery; whereas turbulence may not be a feature of this flow field. Whether the spiraling of flow that we observed related to the spiral distribution of early atheroma reported by others, is undetermined.

Animals↗